European Patent Application No. 0 038 756 to Deutsch and Glavan discloses cationic lipophilic complexes of technetium-99m that are useful as negative heart imaging agents in that they accumulate in the normal heart and visualize an infarct as a cold area on a relatively hot background of normal tissue.
The subject complexes of technetium-99m have lipophilic ligands and an overall cationic charge and are described by the formula EQU [(L).sub.2.sup.99m Tc(X).sub.2 ].sup..sym. X.sup..crclbar.,
wherein each L represents the same or different lipophilic ligand strongly chelating for a technetium-99m cation, and wherein the three X's are the same or different monovalent anionic ligand. Examples of such complexes include 99m-Tc(diars).sub.2 X.sub.2.sup.+ wherein diars is o-C.sub.6 H.sub.4 (As(CH.sub.3).sub.2).sub.2 (o-phenylenebis (dimethylarsine)) and X.sub.2 is Cl or Br, trans-99m-Tc(dmpe).sub.2 Cl.sub.2.sup.+ (wherein dmpe is (CH.sub.3).sub.2 P-CH.sub.2 CH.sub.2 -P(CH.sub.3).sub.2) which is said to be the preferred myocardial imaging agent and 99m-Tc(tetraphos)Cl.sub.2.sup.+ (wherein tetraphos is P(CH.sub.2 CH.sub.2 P(C.sub.6 H.sub.5).sub.2).sub.3).
The above-described complexes are prepared by Deutsch and Glavan using the following procedure. The ligand and technetium-99m (in the form of pertechnetate ion or reduced derivative thereof) are first complexed in a mono- or biphasic system employing a large (preferably greater than ten fold) excess of lipophilic ligand over technetium. The resulting complex is isolated and purified using standard chromatographic techniques. Finally, the "purified" complex is dissolved (or suspended) in a pharmacologically acceptable administration vehicle. Among the vehicles suggested by Deutsch and Glavan are saline, 50/50 ethanol/saline, vehicles wherein the concentration of ethanol is varied, vehicles wherein ethanol is replaced by other organic portions such as propylene glycol, glycerol or dimethyl sulfoxide, or vehicles based on solubilization of the radiopharmaceutical in micelles.